Erlotinib, Modified FOLFOX6, and Bevacizumab as First-Line Therapy Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Smitha Krishnamurthi, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00118261
First received: July 8, 2005
Last updated: August 31, 2012
Last verified: August 2012

July 8, 2005
August 31, 2012
March 2005
January 2011   (final data collection date for primary outcome measure)
Number of patients that develop study drug related toxicity [ Time Frame: 3 courses (6 weeks) ] [ Designated as safety issue: Yes ]
Dose-limiting toxicities will be tracked in the first three cycles. The occurrence of DLT in 2 of the first 6 patients, 3 of the first 9 patients, or 4 of the first 12 patients (whichever occurs soonest)will require that subsequent patients are enrolled to the study at 100 mg erlotinib daily.
Not Provided
Complete list of historical versions of study NCT00118261 on ClinicalTrials.gov Archive Site
  • Patient Response to Treatment Measured by RECIST Criteria [ Time Frame: 3 courses (6 weeks) ] [ Designated as safety issue: No ]
    The overall response is the number of participants who experience a confirmed complete (CR) or partial response (PR) of the total analysis population. Per the Response Evaluation Criteria In Solid Tumors (RECIST): CR = all detectable tumor has disappeared, PR = a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum, Progressive disease (PD) = a >=20% increase in target lesions, Stable Disease = small changes that do not meet previously given criteria.
  • Number of patients that can increase the erlotinib dose to 200mg [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    The number of patients requiring an increase in erlotinib dose to 200 mg will be reported as well as the toxicities observed at 200 mg daily erlotinib, the median onset to grade 2 or higher rash and diarrhea at 200 mg erlotinib, and the number of patients requiring a decrease in erlotinib from 200 mg.
Not Provided
Not Provided
Not Provided
 
Erlotinib, Modified FOLFOX6, and Bevacizumab as First-Line Therapy Metastatic Colorectal Cancer
A Phase IB Study in Patients With Metastatic Colorectal Cancer to Evaluate Pharmacodynamic Effects of Erlotinib and Safety and Efficacy of Erlotinib in Combination With Modified FOLFOX6 (mFOLFOX6) and Bevacizumab

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib may help chemotherapy work better by making tumor cells more sensitive to the drugs. Giving erlotinib together with combination chemotherapy and bevacizumab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given together with combination chemotherapy and bevacizumab as first-line therapy in treating patients with metastatic colorectal cancer.

OBJECTIVES:

  • Determine the toxicity of erlotinib, mFOLFOX6, and bevacizumab in patients with metastatic colorectal cancer.
  • Determine the efficacy of this regimen in these patients.
  • Determine the feasibility of escalating the dose of erlotinib in order to maximize the likelihood of developing a grade 2 skin rash in select patients.

OUTLINE: This is a multicenter study.

  • Single-agent erlotinib: Patients receive oral erlotinib once daily on days 1-14 (course 1).
  • Erlotinib, modified FOLFOX6, and bevacizumab chemotherapy: Patients receive oral erlotinib* once daily on days 1-14, oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2 in course 2. Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

NOTE: Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Colorectal Cancer
  • Biological: bevacizumab
    Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • Drug: erlotinib hydrochloride
    Courses 1-3: oral erlotinib once daily on days 1-14. Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • Drug: fluorouracil
    Starting with course 2: fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • Drug: leucovorin calcium
    Starting with course 2: Leucovorin calcium IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • Drug: oxaliplatin
    Starting with course 2: oxaliplatin IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Experimental: Erlotinib, modified FOLFOX6, and bevacizumab
Interventions:
  • Biological: bevacizumab
  • Drug: erlotinib hydrochloride
  • Drug: fluorouracil
  • Drug: leucovorin calcium
  • Drug: oxaliplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
17
January 2011
January 2011   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer

    • Biopsy-accessible metastatic disease
  • Measurable disease
  • No CNS metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 3 months

Hematopoietic

  • WBC ≥ 4,000/mm^3 OR
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL
  • No bleeding disorder

Hepatic

  • Bilirubin ≤ 1.5 mg/dL
  • Albumin ≥ 2.5 g/dL

Renal

  • Creatinine ≤ 1.5 mg/dL
  • Urine protein:creatine ratio < 1.0

Cardiovascular

  • Blood pressure ≤ 150/100 mmHg
  • No arterial thrombotic event within the past 6 months
  • No New York Heart Association grade II-IV congestive heart failure

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 month after completion of study treatment
  • No other malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other malignancy with < 10% chance of relapse within 3 years
  • No uncontrolled infection
  • No severe uncontrolled illness that would preclude study participation
  • No peripheral neuropathy interfering with function
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious non-healing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy
  • No concurrent sargramostim (GM-CSF)

Chemotherapy

  • No prior chemotherapy, including oxaliplatin, for metastatic disease
  • Prior adjuvant oxaliplatin allowed provided disease progressed > 12 months after completion of oxaliplatin
  • At least 3 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas)

    • No more than 2 courses of prior mitomycin
  • No concurrent chemotherapy

Endocrine therapy

  • No concurrent anticancer hormonal therapy

Radiotherapy

  • At least 2 weeks since prior radiotherapy
  • No prior radiotherapy to > 15% of bone marrow
  • No concurrent radiotherapy

Surgery

  • At least 4 weeks since prior major surgery
  • At least 1 week since prior minor surgery

Other

  • Recovered from prior therapy
  • No prior epidermal growth factor receptor inhibitor therapy
  • No other concurrent antineoplastic or antitumor therapy
  • No other concurrent investigational agents
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00118261
CASE2204, P30CA043703, CASE2204, NCI-2009-01287
Yes
Smitha Krishnamurthi, Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Smitha Krishnamurthi, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP